Human red blood cells (RBC's) from 400 to 500 individuals will be obtained by random selection from a population of blood donors and assayed in vitro for lithium ion transport parameters. These parameters include the RBC lithium ion ratio and the activity of the sodium-lithium countertransport system. The population studies will lead to Family studies involving about 50 families that are selected on the basis of a distinguishing characteristic of a proband (e.g. high or low RBC lithium ion ratio). The object of these studies is to determine whether the variations in RBC lithium ion ratio and the sodium-lithium countertransport system are determined by mendelian (monogenic) inheritance. This research will lead to a similar study on a population of manic depressive patients to determine whether these patients differ in these parameters from the random population.